Abstract The candidate, Yewande Taiwo, is an African-American biomedical engineer, having recently completed her undergraduate degree in biomedical engineering at Illinois Institute of Technology, followed by her master?s degree in biomedical engineering at Washington University in St. Louis. Her coursework within biomedical engineering was focused on neuroscience and neuroimaging. By way of the NIH NHLBI Diversity Supplement, she is seeking one year of mentored training in clinical neuroimaging research to strengthen her application to PhD programs in biomedical engineering and to solidify her career trajectory towards using her biomedical engineering expertise to advance knowledge and treatments for neurological and psychiatric diseases. Her primary mentor and PI of the parent award is Dr. Andria Ford who will be able to train Yewande in all aspects of clinical research, with expertise in vascular neurology, sickle cell disease, and cerebral flow and metabolism. Her co-mentor and co-investigator on the parent award is Dr. Hongyu An who will be able to train Yewande in all aspects of neuroimaging methods, both routine and advanced, as well as neuroimage processing and analysis. Dr. Ford and Dr. An have designed a career training and mentoring plan to help Yewande complete her goal to successfully apply and enter a PhD program in biomedical engineering, with planned application in the 2019 for entry in Spring 2020. Yewande is originally from Nigeria, but became a U.S. Citizen at a young age, moving to the U.S. at age 3. She is passionate about Dr. Ford?s research program in sickle cell disease, not only because the focus is on neuroimaging, but also because sickle cell disease is prevalent in Nigeria, much more common in Africa compared to the U.S. The scientific aims of the supplemental research proposal will evaluate the ability of cerebral blood flow and oxygen extraction fraction, as indices of hemodynamic and metabolic stress, respectively, to predict disruption of white matter integrity as measured by diffusion tensor imaging (DTI) in normal appearing white matter that is unaffected by silent infarcts. The research proposal falls within the scope of the parent award, in that the parent award evaluated CBF and OEF as predictors of development of silent and overt infarcts. Several lines of research have shown that disruption of white matter integrity is a precursor to silent cerebral infarcts or ?white matter disease? in aging/hypertension associated cerebral small vessel disease. Thus, the supplemental award will continue and add more confidence to the overarching goals of the parent R01 to evaluate CBF and OEF as predictors of chronic cerebral ischemia in SCD. Aim 1. To determine if elevation in CBF and/or OEF are associated with disruption in white matter integrity in normal appearing white matter, unaffected by silent cerebral infarction. Aim 2. To determine if disruption in white matter integrity is accelerated in children with SCD compared to normal healthy children. With completion of the above aims, our findings will demonstrate that CBF and/or OEF provide tissue-specific biomarkers for structural injury prior to development of silent cerebral infarction in pediatric SCD. Further, we will begin to define a time-course starting with oxygen metabolic stress, leading to disruption of white matter integrity, leading to silent infarction in pediatric SCD.